Gene delivery system having enhanced tumor-specific expression, and recombinant gene expression regulating sequence

Abstract

The present invention relates to a gene expression regulating sequence consisting of a combination of HRE, E2F and TERT, and to a gene delivery system having significantly improved selective tumor cell cytotoxicity using same, and more particularly, to a recombinant adenovirus. In addition, the present invention relates to a pharmaceutical antitumor composition comprising the recombinant adenovirus. The replication of the recombinant adenovirus of the present invention is tumor-specifically regulated by the novel gene expression regulating sequence of the present invention, thus enabling the recombinant adenovirus of the present invention to exhibit improved selective tumor cell cytotoxicity or apoptotic potential, and exhibit remarkably improved antitumor effects particularly in hypoxic conditions. In addition, the specific expression of the recombinant adenovirus in tumor cells may increase in vivo stability, and thus may induce greatly improved antitumor effects.

Description

CROSS REFERENCE TO RELATED APPLICATIONS AND CLAIM OF PRIORITY[0001]This patent application is a National Phase application under 35 U.S.C. §371 of International Application No. PCT / KR2011 / 004693, filed on Jun. 28, 2011, which claims priority to Korean Patent Application number 10-2010-0098498, filed on Oct. 8, 2010, entire contents of which are incorporated herein by reference.REFERENCE TO A SEQUENCE LISTING[0002]This application contains references to nucleic acid sequences which have been submitted concurrently herewith as the sequence listing text file “61652987_1.txt”, file size 2 KiloBytes (KB), created on 4 Jan. 2016. The aforementioned sequence listing is hereby incorporated by reference in its entirety pursuant to 37 C.F.R. §1.52(e)(5).FIELD OF THE INVENTION[0003]The present invention relates to a gene delivery system having a recombinant gene expression regulatory sequence with improved tumor-specific expression.DESCRIPTION OF THE RELATED ART[0004]A growth of malignant tumo...

AI Technical Summary

Benefits of technology

[0008]The present inventors have made intensive researches to develop a therapeutic agent with better improved oncolytic activity through excellent tumor-specific gene delivery efficiency. As a result, they have found that where adenovirus including expression regulatory sequence consisting of a HRE enhancer, an E2F promoter and a TERT promoter is used, oncolytic activity is significantly increased.

[0009]Accordingly, it is an object of this invention to provide a gene delivery system with improved tumor-specific expression.

[0010]It is another object of this invention to provide a recombinant adenovirus with improved oncolytic activity.

Problems solved by technology

It turns out that persistent tumor treatments using virus are limited.

Blood supply in most of tumor cells is insufficient since tumor cells typically grow faster than endothelial cells generating blood vessels such that hypoxia is induced in tumor cells.

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